Virus turns bacteria’s defenses against them

The enemy of my enemy is my friend.

The “evolutionary arms race” that is immunity extends even to bacteria and the viruses that infect them.

It is hardly news that viruses change to evade our immune systems; we know this all too well from HIV and influenza. It turns out that bacteriophages—viruses that infect bacteria—can do the same thing. Bacteria have many innate immune strategies to protect themselves against phage, but we only know of one that can adapt to attack different viruses. Turns out that some phages "know" about it too—and can change to avoid it, thus destroying the bacteria and ensuring the production of more phage.

The only documented bacterial adaptive immune system is the CRISPR/Cas system (That stands for Clustered Regularly Interspaced Short Palindromic Repeats/CRISPR-associated proteins). These are regions of DNA consisting of a short sequence repeated a number of times, with the repeats separated by a spacer region of DNA. The spacers contain copies of fragments of DNA from phage that have attacked the bacteria in the past.

This is what is supposed to happen is that when phages invade: the repeat elements are made into RNA that matches the phage’s nucleic acids, signaling the bacteria to the presence of the foreign genetic material and inducing the destruction of the phage “through an unknown mechanism.” But some phage have found away around that.

Vibrio cholera bacteria has a phage called ICP1 that was isolated from the diarrhea of cholera patients in Bangladesh. ICP1 uses its own CRISPR/Cas system to destroy the bacteria’s version. And when researchers mutated either the phage’s or the bacteria’s CRISPR/Cas sequences so the length of the spacers didn’t match, succeeding generations of phage mutated to incorporate an appropriate spacer so they could successfully knock out the bacteria's protections and infect it.

CRISPR-like arrays aren't limited to cholera-causing bacteria. Clostidium difficile, a strain of bacteria that causes severe diarrhea, also has one. If we could find a bacteriophage to fight C. difficile, it might provide a more palatable therapy than fecal transplants.

In a bygone age we set the stageFor superbug mutationsWe pit our brains against those strainsWith 20 minute generationsCos we saved some dead with mouldy breadAnd surgeries enhancedWe have the sense that intelligenceMakes us the more advancedBut now's the part where we're not so smartAnd realise our deepest fearsWe've met our match; our current catchHas been here for 4 billion yearsThey've fought for life through greater strifeThan humans can realise(And for what it's worth terraformed EarthFrom Hell to Paradise)They'll make their home where we can't roamIn the air or earth or seaThey evolved a race to take 'em to spaceA member of which is me!On topic now; we're learning howThese superbeings dealWith the viral horde; a dna record - Now this shit just got real...

In a bygone age we set the stageFor superbug mutationsWe pit our brains against those strainsWith 20 minute generationsCos we saved some dead with mouldy breadAnd surgeries enhancedWe have the sense that intelligenceMakes us the more advancedBut now's the part where we're not so smartAnd realise our deepest fearsWe've met our match; our current catchHas been here for 4 billion yearsThey've fought for life through greater strifeThan humans can realise(And for what it's worth terraformed EarthFrom Hell to Paradise)They'll make their home where we can't roamIn the air or earth or seaThey evolved a race to take 'em to spaceA member of which is me!On topic now; we're learning howThese superbeings dealWith the viral horde; a dna record - Now this shit just got real...

The Internet could use more of this and less bickering about pictures of cats. Excellent write up as well!

A replacement for antibiotics? Viruses that target bacterial infections?

The Russians (used?) to do this. Phage Therapy is a bit more difficult, and more expensive, but it does have the great advantage that unlike antibiotics, you have evolution working on your side as well, rather than just against you.

Bacteria WILL evolve, share, and swap antibiotic resistances, but at the same time, the Viruses that parasitize them WILL evolve ways around their defenses, and there's always plenty of viruses to do the evolving.

In the long run, I think its fairly likely that we'll have to turn towards phage therapy more and more, assuming that the antibiotic situation doesn't drastically improve.

The phage would need to survive the acidic conditions of the stomach, as well as the various enzymes and detergents in the digestive system. Not impossible, but not trivial either.

Phage therapy is older than antibiotics.

Well it is older, but it hasn't worked nearly as well. Maybe now it will with faster identification of bacteria strains it will work better. Remember, each phage is only good for one specific bacteria, antibiotics usually cover multiple so you can cover a broad spectrum immediately with a few antibiotics before you know what the bacteria is. The biggest problem is going to be that phage are fairly limited to gut and topical uses. If you inject them they will be treated as foreign protein and they will be cleared or cause allergic reactions.

Isn't there a risk that if a virus is introduced to fight the bacteria, that the virus might decide you yourself are a pretty nice home?

Risk is extremely low as phages have the most limited toolkit in biology. Typically a protein coat evolved to interact with a specific protein on the surface of the host (bacteria) which surrounds a genome which can be DNA or RNA (if its RNA the the virus is termed a retrovirus). It then uses that protein/viral coat to gain access to the interior of the bacteria where it co-opts the DNA or RNA to manufacture more genetic material like its own. The virus have evolved to have the most limited amount of equipment that can still replicate. No cells, no organelles, no energy generating equipment. They require a host to to replicate. The hosts tend to be very limited in scope. A tobacco mosaic virus (TMV) attacks tobacco and a few other plants that are closely related, and virtually nothing else. See the wikipedia article on TMV.

The phage would need to survive the acidic conditions of the stomach, as well as the various enzymes and detergents in the digestive system. Not impossible, but not trivial either.

Or it could be delivered as a suppository . . . no more convenient than fecal transplants, but perhaps easier to standardize.

People seem to be forgetting the fact that fecal transplants are meant to re-introduce the balance between C.diff and the other bateria, not get rid of the C.diff completely. C. diff diarrhea is caused by killing off 1+ types of other bacteria allowing C. diff to over colonize the gastrointestinal tract. Introducing a mutated bacteriophage to wipe out said bacterium just doesn't seem like a solid move, because it would just allow over colonization by some other species.

I have been saying for years they should just change the name of fecal transplant to microbiota transplant or something. If they changed the name no one would give a .........shit.